Mucosal-associated invariant T (MAIT) cells are unconventional T cells that recognize microbial riboflavin pathway metabolites presented by evolutionarily conserved MR1 molecules. We explored the human MAIT cell compartment across organ donor–matched blood, barrier, and lymphoid tissues. MAIT cell population size was donor dependent with distinct tissue compartmentalization patterns and adaptations: Intestinal CD103 + resident MAIT cells presented an immunoregulatory CD39 high CD27 low profile, whereas MAIT cells expressing NCAM1/CD56 dominated in the liver and exhibited enhanced effector capacity with elevated response magnitude and polyfunctionality. Both intestinal CD39 high and hepatic CD56 + adaptations accumulated with donor age. CD56 + MAIT cells displayed limited T cell receptor–repertoire breadth, elevated MR1 binding, and a transcriptional profile skewed toward innate activation pathways. Furthermore, CD56 was dynamically up-regulated to a persistent steady-state equilibrium after exposure to antigen or IL-7. In summary, we demonstrate functional heterogeneity and tissue site adaptation in resident MAIT cells across human barrier tissues with distinct regulatory and effector signatures.

中文翻译：

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配对人体组织中的 MAIT 细胞异质性揭示了不同调节和增强效应谱的专业化


粘膜相关不变 T (MAIT) 细胞是非常规 T 细胞，可识别由进化保守的 MR1 分子呈现的微生物核黄素途径代谢物。我们探索了器官供体匹配的血液、屏障和淋巴组织中的人类 MAIT 细胞区室。 MAIT 细胞群大小取决于供体，具有不同的组织区室化模式和适应性：肠道 CD103 + 驻留 MAIT 细胞呈现免疫调节 CD39 高 CD27 低分布，而表达 NCAM1/CD56 的 MAIT 细胞在肝脏中占主导地位，并表现出增强的效应能力和升高的反应幅度和多功能性。肠道 CD39 高值和肝脏 CD56 + 适应值均随着供体年龄的增长而积累。 CD56 + MAIT 细胞表现出有限的 T 细胞受体库广度、MR1 结合升高以及偏向先天激活途径的转录谱。此外，暴露于抗原或 IL-7 后，CD56 动态上调至持续稳态平衡。总之，我们证明了人类屏障组织中常驻 MAIT 细胞的功能异质性和组织位点适应性，具有不同的调节和效应特征。